Chronic rhinosinusitis (CRS) is estimated to affect 31 million American and lead to 12.5 million physician office visits and $4.3 billion in healthcare costs each year. Yet, CRS management and diagnosis remain consensus-based. Currently, patients are diagnosed with CRS by a combination of symptoms lasting for e 12 weeks, confirmed with clinical findings. First-line CRS therapy consists of a combination of empiric systemic antibiotic therapy with topical or oral steroid therapy, which has been associated with increased antibiotic-resistance in patients with CRS. To improve effectiveness of CRS management and to minimize the unnecessary use of broad-spectrum antibiotics, elucidation of the contribution of host inflammatory response and microbial pathogens in CRS pathogenesis is essential. The long-term goal of our research is to determine the role of sinus microbiota in CRS pathogenesis. The central hypothesis of this proposal is that sinus inflammation-likely resulting from dysregulated host mucosal immune function-precedes and drives the change in the sinus microbiota. In our preliminary assessment of the sinus bacterial microbiota in control and CRS subjects with and without nasal polyposis (CRSwNP and CRSsNP, respectively) using 16S rRNA gene-based pyrosequencing, we detected a greater than expected level of bacterial diversity in both groups and unique trends in microbiota in each group of interest. We also found two potential microbiota core types in the paranasal sinus: a diverse versus a single- bacteria dominated microbiota. The prevalence of single-bacteria dominated microbiota was highest in the non-treated CRSwNP patients, followed by post-corticosteroids CRSwNP patients, CRSsNP, and controls. This led us to hypothesize that we will be able to demonstrate unique, albeit potentially overlapping, microbiota types in each patient group (SA-1). We further hypothesized that by comparing prospectively collected pre- and post-treatment samples from CRSwNP patients, we will be able to detect a shift from CRSwNP microbiota towards non-CRS microbiota (SA-2). Our proposed research will achieve one of the primary objectives of the Human Microbiome Project, which seeks to elucidate the association between microbiota and human health and disease. The collaboration between an academic institution (NAU), a non-profit translational research institute (TGen), and an academic clinical department (Johns Hopkins) is uniquely qualified to perform the proposed research and to provide NAU students with exposure to meritorious biomedical research, as well as to enhance the research environment at NAU. PUBLIC HEALTH RELEVANCE: Chronic rhinosinusitis (CRS) is a common and costly inflammatory disease that is usually treated with oral antibiotics, which has been associated with an increase in antibiotic-resistance. Yet, we do not fully understand the role of bacteria in the development of CRS. In this study, we will use molecular methods to compare the bacterial community in the healthy and diseased sinus and study the impact of controlling inflammation on the sinus bacterial community.